Resveratrol in Various Pockets: A Review

Author(s): Ritu Kataria , Anurag Khatkar* .

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 2 , 2019

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Abstract:

Several phenolic compounds bind to proteins (such as enzymes) and interfere in their catalytic mechanism. Interaction studies of natural polyphenol; Resveratrol with various targets like with tubulin, protein kinase C alpha (PKCα), phosphodiesterase-4D, human oral cancer cell line proteins, DNA sequences having AATT/TTAA segments, protein kinase C alpha, lysine-specific demethylase 1 have been reviewed in this article. Simulation studies indicate that resveratrol and its analogs/ derivatives show good interaction with the target receptor through its hydroxyl groups by forming hydrogen bonds and hydrophobic interactions with amino acid residues at the binding site. Binding geometry and stability of complex formed by resveratrol show that it is a good inhibitor for many pathogenic targets. Further studies in this direction is, however, the need of the hour to develop many more ligands based on resveratrol skeleton which can further serve in the treatment of ailments.

Keywords: Resveratrol, Molecular Docking, Anticancer, Urease inhibition, Protein kinase C alpha, AATT/TTAA.

[1]
Nakao, S.; Mabuchi, M.; Wang, S.; Kogure, Y.; Shimizu, T.; Noguchi, K.; Tanaka, A.; Dai, Y. Synthesis of resveratrol derivatives as new analgesic drugs through desensitization of the TRPA1 receptor. Bioorg. Med. Chem. Lett., 2017, 27(14), 3167-3172.
[http://dx.doi.org/10.1016/j.bmcl.2017.05.025] [PMID: 28576617]
[2]
Baur, J.A.; Sinclair, D.A. Therapeutic potential of resveratrol: The in vivo evidence. Nat. Rev. Drug Discov., 2006, 5(6), 493-506.
[http://dx.doi.org/10.1038/nrd2060] [PMID: 16732220]
[3]
Kolahdouz Mohammadi, R.; Arablou, T. Resveratrol and endometriosis: In vitro and animal studies and underlying mechanisms (Review). Biomed. Pharmacother., 2017, 91, 220-228.
[http://dx.doi.org/10.1016/j.biopha.2017.04.078] [PMID: 28458160]
[4]
Guerrero, R.F.; García-Parrilla, M.C.; Puertas, B.; Cantos-Villar, E. Wine, resveratrol and health: A review. Nat. Prod. Commun., 2009, 4(5), 635-658.
[PMID: 19445315]
[5]
Chen, A.C.; Shyu, L.Y.; Hsin, Y.L.; Chen, K.M.; Lai, S.C. Resveratrol relieves Angiostrongylus cantonensis-Induced meningoencephalitis by activating sirtuin-1. Acta Trop., 2017, 173, 76-84.
[http://dx.doi.org/10.1016/j.actatropica.2017.05.023] [PMID: 28545897]
[6]
Nakata, R.; Takahashi, S.; Inoue, H. Recent advances in the study on resveratrol. Biol. Pharm. Bull., 2012, 35(3), 273-279.
[http://dx.doi.org/10.1248/bpb.35.273] [PMID: 22382311]
[7]
Wang, Y.; Sun, J.; Chen, L.; Zhou, S.; Lin, H.; Wang, Y.; Lin, N.; Ge, R.S. Effects of resveratrol on rat neurosteroid synthetic enzymes. Fitoterapia, 2017, 122, 61-66.
[http://dx.doi.org/ 10.1016/j.fitote.2017.08.005] [PMID: 28823883]
[8]
Singh, I.; Goyal, Y.; Ranawat, P. Potential chemoprotective role of resveratrol against cisplatin induced testicular damage in mice. Chem. Biol. Interact., 2017, 273, 200-211.
[http://dx.doi.org/ 10.1016/j.cbi.2017.05.024] [PMID: 28606469]
[9]
Duan, W.J.; Li, Y.F.; Liu, F.L.; Deng, J.; Wu, Y.P.; Yuan, W.L.; Tsoi, B.; Chen, J.L.; Wang, Q.; Cai, S.H.; Kurihara, H.; He, R.R.A. SIRT3/AMPK/autophagy network orchestrates the protective effects of trans-resveratrol in stressed peritoneal macrophages and RAW 264.7 macrophages. Free Radic. Biol. Med., 2016, 95, 230-242.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.03.022] [PMID: 27021965]
[10]
Gobec, M.; Tomašič, T.; Markovič, T.; Mlinarič-Raščan, I.; Dolenc, M.S.; Jakopin, Ž. Antioxidant and anti-inflammatory properties of 1,2,4-oxadiazole analogs of resveratrol. Chem. Biol. Interact., 2015, 240, 200-207.
[http://dx.doi.org/10.1016/j.cbi.2015.08.018] [PMID: 26335192]
[11]
Gerszon, J.; Rodacka, A.; Puchała, M. Antioxidant properties of resveratrol and its protective effects in neurodegenerative diseases. Adv. Cell Biol., 2014, 4(2), 97-117.
[http://dx.doi.org/10.2478/acb-2014-0006]
[12]
Fauconneau, B.; Waffo-Teguo, P.; Huguet, F.; Barrier, L.; Decendit, A.; Merillon, J.M. Comparative study of radical scavenger and antioxidant properties of phenolic compounds from Vitis vinifera cell cultures using in vitro tests. Life Sci., 1997, 61(21), 2103-2110.
[http://dx.doi.org/10.1016/S0024-3205(97)00883-7] [PMID: 9395251]
[13]
Waffo-Téguo, P.; Hawthorne, M.E.; Cuendet, M.; Mérillon, J.M.; Kinghorn, A.D.; Pezzuto, J.M.; Mehta, R.G. Potential cancer-chemopreventive activities of wine stilbenoids and flavans extracted from grape (Vitis vinifera) cell cultures. Nutr. Cancer, 2001, 40(2), 173-179.
[http://dx.doi.org/10.1207/S15327914NC402_14] [PMID: 11962253]
[14]
Rius, C.; Abu-Taha, M.; Hermenegildo, C.; Piqueras, L.; Cerda-Nicolas, J.M.; Issekutz, A.C.; Estañ, L.; Cortijo, J.; Morcillo, E.J.; Orallo, F.; Sanz, M.J. Trans- but not cis-resveratrol impairs angiotensin-II-mediated vascular inflammation through inhibition of NF-κB activation and peroxisome proliferator-activated receptor-gamma upregulation. J. Immunol., 2010, 185(6), 3718-3727.
[http://dx.doi.org/10.4049/jimmunol.1001043] [PMID: 20709957]
[15]
Trela, B.C.; Waterhouse, A.L. Resveratrol: Isomeric molar absorptivities and stability. J. Agric. Food Chem., 1996, 44(5), 1253-1257.
[http://dx.doi.org/10.1021/jf9504576]
[16]
Wang, T.T.; Schoene, N.W.; Kim, Y.S.; Mizuno, C.S.; Rimando, A.M. Differential effects of resveratrol and its naturally occurring methylether analogs on cell cycle and apoptosis in human androgen-responsive LNCaP cancer cells. Mol. Nutr. Food Res., 2010, 54(3), 335-344.
[http://dx.doi.org/10.1002/mnfr.200900143] [PMID: 20077416]
[17]
Singh, I.; Goyal, Y.; Ranawat, P. Potential chemoprotective role of resveratrol against cisplatin induced testicular damage in mice. Chem. Biol. Interact., 2017, 273, 200-211.
[http://dx.doi.org/ 10.1016/j.cbi.2017.05.024] [PMID: 28606469]
[18]
Langcake, P.; Pryce, R.J. The production of resveratrol by Vitis vinifera and other members of the Vitaceae as a response to infection or injury. Physiol. Plant Pathol., 1976, 9(1), 77-86.
[http://dx.doi.org/10.1016/0048-4059(76)90077-1]
[19]
Seidman, M.; Babu, S.; Tang, W.; Naem, E.; Quirk, W.S. Effects of resveratrol on acoustic trauma. Otolaryngol. Head Neck Surg., 2003, 129(5), 463-470.
[http://dx.doi.org/10.1016/S0194-5998(03)01586-9] [PMID: 14595267]
[20]
Silva, R.C.D.; Teixeira, J.A.; Nunes, W.D.G.; Zangaro, G.A.C.; Pivatto, M.; Caires, F.J.; Ionashiro, M. Resveratrol: A thermoanalytical study. Food Chem., 2017, 237, 561-565.
[http://dx.doi.org/10.1016/j.foodchem.2017.05.146] [PMID: 28764035]
[21]
Fan, E.; Zhang, K.; Zhu, M.; Wang, Q. Obtaining resveratrol: From chemical synthesis to biotechnological production. Mini Rev. Org. Chem., 2010, 7(4), 272-281.
[http://dx.doi.org/10.2174/157019310792246454]
[22]
Trantas, E.; Panopoulos, N.; Ververidis, F. Metabolic engineering of the complete pathway leading to heterologous biosynthesis of various flavonoids and stilbenoids in Saccharomyces cerevisiae. Metab. Eng., 2009, 11(6), 355-366.
[http://dx.doi.org/10.1016/j.ymben.2009.07.004] [PMID: 19631278]
[23]
Kolahdouz Mohammadi, R.; Arablou, T. Resveratrol and endometriosis: In vitro and animal studies and underlying mechanisms (Review). Biomed. Pharmacother., 2017, 91, 220-228.
[http://dx.doi.org/10.1016/j.biopha.2017.04.078] [PMID: 28458160]
[24]
Brown, V.A.; Patel, K.R.; Viskaduraki, M.; Crowell, J.A.; Perloff, M.; Booth, T.D.; Vasilinin, G.; Sen, A.; Schinas, A.M.; Piccirilli, G.; Brown, K.; Steward, W.P.; Gescher, A.J.; Brenner, D.E. Repeat dose study of the cancer chemopreventive agent resveratrol in healthy volunteers: safety, pharmacokinetics, and effect on the insulin-like growth factor axis. Cancer Res., 2010, 70(22), 9003-9011.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-2364] [PMID: 20935227]
[25]
Kim, S.; Jin, Y.; Choi, Y.; Park, T. Resveratrol exerts anti-obesity effects via mechanisms involving down-regulation of adipogenic and inflammatory processes in mice. Biochem. Pharmacol., 2011, 81(11), 1343-1351.
[http://dx.doi.org/10.1016/j.bcp.2011.03.012] [PMID: 21439945]
[26]
Park, S.J.; Ahmad, F.; Philp, A.; Baar, K.; Williams, T.; Luo, H.; Ke, H.; Rehmann, H.; Taussig, R.; Brown, A.L.; Kim, M.K.; Beaven, M.A.; Burgin, A.B.; Manganiello, V.; Chung, J.H. Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell, 2012, 148(3), 421-433.
[http://dx.doi.org/10.1016/j.cell.2012.01.017] [PMID: 22304913]
[27]
Witte, A.V.; Kerti, L.; Margulies, D.S.; Flöel, A. Effects of resveratrol on memory performance, hippocampal functional connectivity, and glucose metabolism in healthy older adults. J. Neurosci., 2014, 34(23), 7862-7870.
[http://dx.doi.org/10.1523/JNEUROSCI.0385-14.2014] [PMID: 24899709]
[28]
Xu, Q.; Si, L.Y. Resveratrol role in cardiovascular and metabolic health and potential mechanisms of action. Nutr. Res., 2012, 32(9), 648-658.
[http://dx.doi.org/10.1016/j.nutres.2012.07.002] [PMID: 23084637]
[29]
Acevedo-Fani, A.; Silva, H.D.; Soliva-Fortuny, R.; Martín-Belloso, O.; Vicente, A.A. Formation, stability and antioxidant activity of food-grade multilayer emulsions containing resveratrol. Food Hydrocoll., 2017, 71, 207-215.
[http://dx.doi.org/ 10.1016/j.foodhyd.2017.05.007]
[30]
Baur, J.A.; Pearson, K.J.; Price, N.L.; Jamieson, H.A.; Lerin, C.; Kalra, A.; Prabhu, V.V.; Allard, J.S.; Lopez-Lluch, G.; Lewis, K.; Pistell, P.J.; Poosala, S.; Becker, K.G.; Boss, O.; Gwinn, D.; Wang, M.; Ramaswamy, S.; Fishbein, K.W.; Spencer, R.G.; Lakatta, E.G.; Le Couteur, D.; Shaw, R.J.; Navas, P.; Puigserver, P.; Ingram, D.K.; de Cabo, R.; Sinclair, D.A. Resveratrol improves health and survival of mice on a high-calorie diet. Nature, 2006, 444(7117), 337-342.
[http://dx.doi.org/10.1038/nature05354] [PMID: 17086191]
[31]
Wang, Y.; Sun, J.; Chen, L.; Zhou, S.; Lin, H.; Wang, Y.; Lin, N.; Ge, R.S. Effects of resveratrol on rat neurosteroid synthetic enzymes. Fitoterapia, 2017, 122, 61-66.
[http://dx.doi.org/ 10.1016/j.fitote.2017.08.005] [PMID: 28823883]
[32]
Das, S.; Ng, K.Y. Resveratrol-loaded calcium-pectinate beads: effects of formulation parameters on drug release and bead characteristics. J. Pharm. Sci., 2010, 99(2), 840-860.
[http://dx.doi.org/ 10.1002/jps.21880] [PMID: 19653272]
[33]
Siddiqui, A.; Dandawate, P.; Rub, R.; Padhye, S.; Aphale, S.; Moghe, A.; Jagyasi, A.; Venkateswara Swamy, K.; Singh, B.; Chatterjee, A.; Ronghe, A.; Bhat, H.K. Novel Aza-resveratrol analogs: synthesis, characterization and anticancer activity against breast cancer cell lines. Bioorg. Med. Chem. Lett., 2013, 23(3), 635-640.
[http://dx.doi.org/10.1016/j.bmcl.2012.12.002] [PMID: 23273518]
[34]
Aldawsari, F.S.; Aguiar, R.P.; Wiirzler, L.A.M.; Aguayo-Ortiz, R.; Aljuhani, N.; Cuman, R.K.N.; Medina-Franco, J.L.; Siraki, A.G.; Velázquez-Martínez, C.A. Anti-inflammatory and antioxidant properties of a novel resveratrol-salicylate hybrid analog. Bioorg. Med. Chem. Lett., 2016, 26(5), 1411-1415.
[http://dx.doi.org/ 10.1016/j.bmcl.2016.01.069] [PMID: 26850006]
[35]
Borriello, A.; Cucciolla, V.; Della Ragione, F.; Galletti, P. Dietary polyphenols: focus on resveratrol, a promising agent in the prevention of cardiovascular diseases and control of glucose homeostasis. Nutr. Metab. Cardiovasc. Dis., 2010, 20(8), 618-625.
[http://dx.doi.org/10.1016/j.numecd.2010.07.004] [PMID: 20850033]
[36]
Szkudelski, T.; Szkudelska, K. Resveratrol and diabetes: From animal to human studies. Biochim. Biophys. Acta, 2015, 1852(6), 1145-1154.
[http://dx.doi.org/10.1016/j.bbadis.2014.10.013]
[37]
Pany, S.; Ghosh, A.; You, Y.; Nguyen, N.; Das, J. Resveratrol inhibits phorbol ester-induced membrane translocation of presynaptic Munc13-1. Biochim. Biophys. Acta, Gen. Subj., 2017, 1861(11 Pt A), 2640-2651.
[http://dx.doi.org/10.1016/j.bbagen.2017.07.006] [PMID: 28713022]
[38]
Ethemoglu, M.S.; Seker, F.B.; Akkaya, H.; Kilic, E.; Aslan, I.; Erdogan, C.S.; Yilmaz, B. Anticonvulsant activity of resveratrol-loaded liposomes in vivo. Neuroscience, 2017, 357, 12-19.
[http://dx.doi.org/10.1016/j.neuroscience.2017.05.026] [PMID: 28577913]
[39]
Ruan, B.F.; Lu, X.; Tang, J.F.; Wei, Y.; Wang, X.L.; Zhang, Y.B.; Wang, L.S.; Zhu, H.L. Synthesis, biological evaluation, and molecular docking studies of resveratrol derivatives possessing chalcone moiety as potential antitubulin agents. Bioorg. Med. Chem., 2011, 19(8), 2688-2695.
[http://dx.doi.org/10.1016/j.bmc.2011.03.001] [PMID: 21440448]
[40]
Pany, S.; Majhi, A.; Das, J. PKC activation by resveratrol derivatives with unsaturated aliphatic chain. PLoS One, 2012, 7(12), e52888.
[http://dx.doi.org/10.1371/journal.pone.0052888] [PMID: 23285216]
[41]
Das, J.; Pany, S.; Majhi, A. Chemical modifications of resveratrol for improved protein kinase C alpha activity. Bioorg. Med. Chem., 2011, 19(18), 5321-5333.
[http://dx.doi.org/10.1016/j.bmc.2011.08.008] [PMID: 21880495]
[42]
Zhao, P.; Chen, S.K.; Cai, Y.H.; Lu, X.; Li, Z.; Cheng, Y.K.; Zhang, C.; Hu, X.; He, X.; Luo, H.B. The molecular basis for the inhibition of phosphodiesterase-4D by three natural resveratrol analogs. Isolation, molecular docking, molecular dynamics simulations, binding free energy, and bioassay. Biochim. Biophys. Acta, 2013, 1834(10), 2089-2096.
[http://dx.doi.org/10.1016/j.bbapap.2013.07.004] [PMID: 23871879]
[43]
Manimaran, M.; Sivakumari, K.; Ashok, K. Molecular docking studies of resveratrol against the human oral cancer cell line proteins (kb cells). Int. J. Curr. Adv. Res., 2015, 4(10), 415-420.
[44]
Nair, M.S.; D’Mello, S.; Pant, R.; Poluri, K.M. Binding of resveratrol to the minor groove of DNA sequences with AATT and TTAA segments induces differential stability. J. Photochem. Photobiol. B, 2017, 170, 217-224.
[http://dx.doi.org/10.1016/j.jphotobiol. 2017.04.016] [PMID: 28445857]
[45]
Duan, Y.C.; Guan, Y.Y.; Zhai, X.Y.; Ding, L.N.; Qin, W.P.; Shen, D.D.; Liu, X.Q.; Sun, X.D.; Zheng, Y.C.; Liu, H.M. Discovery of resveratrol derivatives as novel LSD1 inhibitors: Design, synthesis and their biological evaluation. Eur. J. Med. Chem., 2017, 126, 246-258.
[http://dx.doi.org/10.1016/j.ejmech.2016.11.035] [PMID: 27888721]
[46]
Paulo, L.; Oleastro, M.; Gallardo, E.; Queiroz, J.A.; Domingues, F. Anti-Helicobacter pylori and urease inhibitory activities of resveratrol and red wine. Food Res. Int., 2011, 44(4), 964-969.
[http://dx.doi.org/10.1016/j.foodres.2011.02.017]


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VOLUME: 19
ISSUE: 2
Year: 2019
Page: [116 - 122]
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DOI: 10.2174/1568026619666190301173958
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